The Blood Research Institute (BRI) of BloodCenter of Wisconsin has an established, long-term commitment to blood-related research. Currently 19 Principal Investigators lead research programs in the fields of cardiovascular biology, immunology, stem cell biology, transfusion medicine, control of bleeding and thrombosis. The BRI has had a tradition of research strength in platelet and vascular cell biology and have applied their research findings to the treatment of bleeding disorders, blood diseases, heart attack and stroke. The research programs of many BRI investigators have moved into studies involving various animal models of human disease. Experiments performed in vivo require specialized tools to obtain data under physiological relevant conditions. We request funds to purchase a spinning disk confocal microscope system for intravital imaging to accomplish the research goals described by the major and minor users in this application. Projects initiated by twelve NIH-funded Investigators and those initiated by two new investigators require this instrument to accomplish their research goals. These project titles are: Molecular biology and function of PECAM-1; Molecular mechanisms of platelet activation and adhesion; Biomolecular interactions of FVIII and VWF; Molecular impact of VWF on VWD; Comparative effectiveness in the diagnosis of VWD; Asthma increases vaso-occlusion in sickle cell disease; Nociceptive mechanism underlying sickle cell pain; Negative regulation of platelet activity; Molecular mechanisms of VWF alteration in vitro/vivo; B-cell responses in heparin induced thrombocytopenia; Regulation of the anti- antiangiogenic switch by CD36 in thrombosis; Mechanistic role of CD36 signaling in thrombosis; Association of TFPI with endothelium; The biochemistry and physiology of platelet TFPI; Activated Protein C for Treatment of Radiation Combined Injury; Mechanism of Activated Protein C Action in Sepsis Therapy; Platelet- derived FVIII gene therapy of hemophilia A; Mechanism of kindlin-2 in B3 integrin activation; Platelet Function in Thrombophilia-Associated Placental Vascular Disorder. The spinning disk confocal microscope system will become a part of the newly formed Thrombosis Core Lab at the BRI and will enable scientists to evaluate various experimental parameters that affect blood flow and thrombus formation in live animal models.